title: Nanoscale amphiphilic macromolecules with variable lipophilicity and stereochemistry modulate inhibition of oxidized low-density lipoprotein uptake.
abstract: Amphiphilic macromolecules (AMs) based on carbohydrate domains functionalized with poly(ethylene glycol) can inhibit the uptake of oxidized low density lipoprotein (oxLDL) and counteract foam cell formation, a key characteristic of early atherogenesis. To investigate the influence of lipophilicity and stereochemistry on the AMs' physicochemical and biological properties, mucic acid-based AMs bearing four aliphatic chains (2a) and tartaric acid-based AMs bearing two (2b and 2l) and four aliphatic chains (2g and 2k) were synthesized and evaluated. Solution aggregation studies suggested that both the number of hydrophobic arms and the length of the hydrophobic domain impact AM micelle sizes, whereas stereochemistry impacts micelle stability. 2l, the meso analogue of 2b, elicited the highest reported oxLDL uptake inhibition values (89%), highlighting the crucial effect of stereochemistry on biological properties. This study suggests that stereochemistry plays a critical role in modulating oxLDL uptake and must be considered when designing biomaterials for potential cardiovascular therapies.
authors.affiliation: Department of Chemistry, Rutgers University, Piscataway, New Jersey 08854, USA.
authors.forename: Dawanne E
authors.initials: DE
authors.lastname: Poree
authors.forename: Kyle
authors.initials: K
authors.lastname: Zablocki
authors.forename: Allison
authors.initials: A
authors.lastname: Faig
authors.forename: Prabhas V
authors.initials: PV
authors.lastname: Moghe
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Uhrich
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013400:Sugar Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013644:Tartrates / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D008077:Lipoproteins, LDL; D008823:Micelles; D013400:Sugar Acids; D013501:Surface-Active Agents; D013644:Tartrates; C099252:oxidized low density lipoprotein; D011092:Polyethylene Glycols; C000090:galactaric acid